Chromium has been used as low-cost dietary supplements for the treatment of diabetes and its complications. Vanadium compounds also provide various insulin-like effects, and have shown ability to improve glucose metabolic equilibrium and insulin resistance in Type 1 and Type 2 diabetes. There is a need to develop novel methods for the analysis of the metals in biological fluids to assess chromium deficiency and the effect of chromium and vanadium as adjuvant therapy for diabetes. The frequency of chromium deficiency and effect of chromium and vanadium as adjuvant therapy in the population are unknown in part because reliable measures for assessing their status in humans are limited. Such novel methods are of interest to the National Institutes of Health. The overall goal of the proposed research is to combine a novel pretreatment process for, e.g., blood and urine with metal-selective electrochemical measurements for chromium and vanadium in the biological fluids. This application is based on a novel method explored in Dr. Xue's current R21 project, and it seeks support to develop this method from the largely proof-of-principle work into methods for chromium and vanadium analyses in biological fluids. These methods combine the Advanced Oxidation Process (AOP) - a combination of hydrogen peroxide and ultraviolet (UV) radiation - and new chemical analyses to: (1) Breakdown biological/organic species to release the metals;(2) Determine the metal concentrations by metal-selective electrochemical methods. An AOP process has been explored to pretreat blood and urine samples, and it led to successful measurements of low-ppb (parts per billion) chromium in blood. The proposed research will develop this novel process into a general, reliable and more efficient method for chromium detection, and expand the method for vanadium analyses. Fundamental chemistry in the AOP reactions and metal-selective analysis will be studied to provide an understanding of the process. The understanding will be used for improving the process. The chemicals used in the process are environmentally benign, and do not generate harmful residuals or by-products. In this R01 application, we plan to develop our largely proof-of-principle work in the current R21 grant into novel methods for Cr and V analyses in biological fluids. AOP pretreatment and the subsequent electrochemical measurement are two integrated steps in the analyses. {The aims of the proposed research are: (1) Develop fast, convenient, and multi-sample AOP pretreatment methods for blood and urine samples;(2) Provide sensitive, easy-to-use electrochemical methods for Cr and V analysis of the AOP-treated samples;(3) Investigate metal-ligand complexes and their interaction with the electrode surface to give a basic understanding needed to optimize the Cr and V analysis.} The new methods are expected to be easier and cheaper to operate than the current techniques for the chemical analyses of these metals in biological fluids. The research results can be applied immediately in the metal analyses in biological fluids, a goal articulated in the NIH program Non-Invasive Methods for Diagnosis and Progression of Diabetes, Kidney, Urological, Hematological and Digestive Diseases (PA Number: PA-07-025). PUBLIC HEALTH RELEVANCE The novel methods proposed here will help determine chromium and vanadium in biological fluids to assess chromium deficiency and the effect of chromium and vanadium as adjuvant therapy for diabetes. The research results can be applied immediately in the analyses of chromium and vanadium in biological fluids, and help their use as dietary supplements for the treatment of diabetes and its complications.